Subject: AIDS Treatment News #100 Date: Apr 12 1990 (1008 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& copyright 1990 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS #100, April 6, 1990 CONTENTS: [items are separated by "*****" for this display] HIV Physicians -- On the Front Line Lisa Capaldini Larry Waites PML Treatment Survey Emprise: Controversy Over Unorthodox-Treatment Database Burroughs Wellcome Seeks Protocol-Secrecy Law AZT Asymptomatic Study Published -- New Push for Early Diagnosis, Treatment KS Information Needed ***** HIV PHYSICIANS -- ON THE FRONT LINE by Denny Smith In the course of pursuing information which could be of use to our readers, AIDS TREATMENT NEWS frequently calls on the experience and expertise of doctors who are familiar with the latest consensus of care for HIV and related diagnoses. For nearly ten years, AIDS-knowledgeable physicians have been facing problems never encountered before, and have been working with their patients to create solutions with and without the benefit of clinical studies. Unfortunately, we hear from many people with HIV or AIDS whose healthcare providers are apparently not current with diagnostic or treatment information. On the one hand, it is easy to understand the difficulty everyone has with absorbing the avalanche of AIDS developments today. On the other, people facing any serious health crisis are entitled to the most precise and comprehensive medicine available. The rights of a patient do not need to conflict with the responsibilities of a physician. But when there seems to be a conflict, each party might consider whether the difference is one of opinion, or of accurate information. We discussed some common questions of HIV diagnosis and treatment with two respected San Francisco physicians -- Drs. Lisa Capaldini and Larry Waites. Dr. Capaldini is an Assistant Clinical Professor of Medicine at the University of California San Francisco, and cares for many people with HIV in her practice on Castro Street. Dr. Waites is a staff physician at Byers, Levin, Santiago and Waites Medical Group, and currently directs a national clinical trial of compound Q for the Project Inform Community Research Alliance. DIAGNOSING: A DISCUSSION WITH LISA CAPALDINI, M. D. The causes of symptoms related to an HIV infection can often be difficult to diagnose quickly and accurately. There may be several reasons for this difficulty: HIV is a relatively new medical challenge; AIDS functions as an umbrella for a wide spectrum of illnesses; the immune deficiency sometimes allows for infectious agents to colonize unexpected sites (such as Pneumocystis carinii in the gastrointestinal tract). AIDS TREATMENT NEWS asked Dr. Capaldini to share some of her clinical diagnostic experience. Following are some highlights of her remarks. Generally, Dr. Capaldini likes to schedule visits with her asymptomatic patients about every three to six months. These visits include a T-4 helper cell count as well as a brief physical exam. Like most HIV-knowledgeable physicians, she recommends considering AZT therapy for patients with helper cell counts below 500. Symptomatic patients should be seen more frequently, usually once a month. Because several symptoms can occur simultaneously or intermittently, Dr. Capaldini encourages her patients to make a list of problems to bring to the appointment. If medications seem to be causing a problem, she asks that they bring the drug packaging with them, to avoid confusing names like ansamycin and ampicillin, and to verify the dosage. The first consideration in targeting the cause of a new symptom is determining whether a disease process or drug reaction is more likely. Many people are already familiar with past allergic reactions to certain drugs, and they should always make such allergies known to all of their healthcare providers. In addition to the common allergies to the penicillin and sulfa family drugs, Dr. Capaldini notes that some AIDS-related drugs, like rifampin for MAI, can provoke reactions which may not look typical, such as fevers and vomiting without a rash. Some drugs may cause side effects which are acceptable temporary risks if both the patient and physician are prepared for them. Aerosol pentamidine treatments, for example, can produce an unpleasant cough which is easily controlled with a bronchodilator. Intravenous pentamidine, on the other hand, has been associated with low blood pressure and low blood sugar during infusion, and transient diabetes in some people after prolonged I. V. therapy. If reactions to medications have essentially been ruled out, then specific possible physical causes are investigated. Generally, physical symptoms are more specific than drug reactions, but also may not present themselves characteristically. Someone with pneumonia may be fatigued but not, as would be expected, short of breath. Unless the attending physician orders a chest x-ray or tests for oxygen saturation in arterial blood gases, a Pneumocystis infection could be overlooked. Fatigue as well as headaches may be due to sinusitis, even without any discharge. Sinus films can help rule out this possibility. Headaches and any focal neurologic symptoms such as confusion or loss of motor skills deserve quick attention; a delay in diagnosing cryptococcal meningitis, or encephalitis caused by Toxoplasma, herpes or CMV infections, can be life- threatening. Other neurologic diseases such as PML infections, KS lesions or lymphoma of the central nervous system may progress more slowly but also present grave consequences without treatment. Some neurologic symptoms are due to primary HIV infection and may respond to AZT alone. Patients whose symptoms evade diagnosis with MRI or CT scans or lumbar punctures should be given a trial of AZT, regardless of their helper cell levels. HIV neurologic symptoms and subtle dementia can occur in some people even in the face of relatively high helper cell counts, although asymptomatic patients should be reassured not to overinterpret isolated moments of forgetfulness. In any event, fatigue and headaches are commonly reported symptoms of HIV infection, and if the urgent critical possibilities have been discarded and AZT alone hasn't helped, Dr. Capaldini considers depression as a cause. She feels that depression as well as panic attacks are much more frequently experienced by HIV+ people than is generally thought. Neuropsychiatric exams can help identify the problems, which in turn often respond to counseling and/or medication. The sight-threatening infection known as CMV retinitis is not necessarily identifiable with the resources of a general practitioner. When patients report floating spots or changes in their field of vision, Dr. Capaldini promptly arranges a consultation with an ophthalmologist, even if a cursory exam appears normal. A delay of just a few days can result in irreversible retinal damage. Toxoplasmosis is another, less frequent cause of vision problems. Skin rashes are often the first signs of an HIV infection progressing to symptoms. Dr. Capaldini suggests to her patients with dermatitis that they use lotions to keep their skin moist, and sometimes offers topical steroid creams for serious problems. Other possibilities to be aware of are eosinophilic folliculitis, scabies, and flare-ups of the herpes zoster virus, or shingles. HIV-related shingles may produce severe pain at nerve endings in the skin, but no rash, and if prescribed early enough, acyclovir is usually effective for preventing the flare-up from getting worse. Skin problems may be misdiagnosed more frequently in people of color, since medical pathology texts are often written and illustrated with a Caucasian bias. Pain in nerve endings, or neuropathy, can also be due to HIV itself, or toxicity from anti-HIV drugs like ddI or ddC. Drug- induced neuropathy may be reversible if the dosage is reduced or put on hold. Dr. Capaldini has obtained some relief for HIV- neuropathy with non-sedating anti-depressants, like nortriptyline. If the neuropathy is affecting the feet, she suggests that they be kept warm. Muscle aches and weakness, or myopathy, may also be due to HIV, or prolonged use of AZT. Discontinuing the drug may clarify the cause of myopathy, which incidentally can be improved or exacerbated by physical exercise. Yeast infections, also called thrush or candidiasis, are frequent problems in people with ARC and AIDS. For women, chronic vaginal yeast infections are often the first symptoms related to HIV, but are often not diagnosed as HIV-related. A Candida infection which has invaded the esophagus is a serious situation, causing pain with swallowing. Dr. Capaldini notes that heartburn per se is not usually due to candidiasis, but rather medications or excess stomach acid. Ulcers in the mouth not related to thrush can be extremely painful but usually respond to elixirs. Extensive ulcers may require a short application of oral prednisone. Diarrhea and weight loss are common HIV-related problems. Diarrhea can be caused by a number of intestinal pathogens, including Mycobacterium avium, Isospora belli, Giardia lamblia and Cryptosporidium . When a stool specimen is sent for standard parasite tests, labs do not always check for the same set of organisms, so the physician may need to specify "Cryptosporidia," for example, on the lab requisition. Unfortunately, some microbes may be present in the intestinal tract without causing symptoms. The isolation of one microbe would not preclude the possibility that the diarrhea is actually resulting from some other infection. In addition to the above organisms, HIV and CMV can both cause colitis. One distinction from viral infections in the intestine is the rapid onset of fevers associated with bacterial infections. HIV can also decrease a tolerance for lactose, so dairy products may complicate a bout of diarrhea. Nausea and weight loss which often are associated with gastrointestinal infections may actually be caused by HIV-impaired motility. Dr. Capaldini suggests Reglan to counter this. Age can influence or disguise symptoms. For example, children with AIDS are prone to recurrent ear infections, but very young children usually cannot articulate the source of their pain. Older people with HIV may already be dealing with health problems which are not necessarily related to the HIV infection. In light of these and many other diagnosis pitfalls, people with HIV need and deserve healthcare provided by HIV-knowledgeable physicians, or physicians willing to learn. Treatment decisions are difficult enough without compounding delays in making a diagnosis. ***** TREATMENT: INTERVIEW WITH LARRY WAITES, M. D. DS: How early would you intervene in an HIV infection? LW: I feel that the 019 (AIDS clinical trials conducted by the NIH) study clearly showed what I've been saying for over two years, which is that asymptomatic people should be treated -- after reviewing the lab data, patient history and physical exam, we start very commonly at 500 T-cells with low-dose AZT, 300 to 600 mg a day. That seemed to be the most effective according to the 019 study. I believe people can often tolerate AZT for more that 18 months, even over two years. Some people are showing signs of resistance after that, but we now have ddI and ddC to go to, so we will be able to leapfrog medicines one after another as resistance develops to any one medicine. There are suggestions as well that we combine some of these drugs, but only limited research has been done on that yet. DS: What about physicians who, in spite of the 019 and 016 studies, continue only to prescribe AZT to people with T-cells under 200 or who have had an opportunistic infection? LW: I think that not giving AZT until the cells are that low is like telling someone with high blood pressure not to get treated until after their first stroke. DS: I'm amazed that some doctors will even state their hesitation publicly. LW: I fully believe that HIV is no different than any other disease, and we've shown over and over that early intervention and prophylactic measures in any chronic illness saves money and saves lives. It boggles my mind that we have to go through this again with HIV disease. This is just a viral illness like any other chronic illness and should be approached the same way. DS: If someone was holding steady at say, 700 helper cells, would you advocate intervention as early as that point? LW: We may come to the point that we treat someone from point zero, as soon as they test positive for HIV, and that the earlier you intervene, the better. Right now, the medicines are so toxic, that I generally do not start people in the 700 range ...I just have to balance the risk and benefit. DS: What kind of blood markers are now useful? LW: Watching the T-cells, and the percent of T-cells, the helper-suppressor ratio, the beta-2 microglobulin, the p24 antigen as well as the p24 antibody. You know the antigen did not previously seem much of a help; not because it didn't measure viral activity, but because the test then wasn't sensitive enough. Now that, for instance, Immunodiagnostic Laboratories has a test which measures down to 10 micrograms per ml, most people who were originally "negative" are now showing up positive; the older tests just weren't sensitive enough. So now with new tests it will be a better marker to watch. I think the p24 antibody (Editor's Note: do not confuse p24 antibody with p24 antigen) probably decreases between 18 months to two years before people get really sick, so we may actually be able to follow the antibody levels in people who are asymptomatic, and identify who should be treated. I had a half-dozen patients whose T-cells were above 400, and were completely asymptomatic, but whose antibodies had dropped to zero. I started them on AZT and their antibodies went up, so my impression is that they were producing both virus and antibodies, and although their antigen levels remained negative, the antibodies were depleted by trying to keep up with the virus. By using an antiviral, we slowed the replication of the virus, and their antibodies increased again because they were less stressed keeping up with the virus. DS: What about neopterin as a marker -- the studies showing a correlation between increases in serum neopterin and disease progression. LW: Oh, we go back and forth about the neopterin; most people aren't taking it seriously because you can find just as many studies which claim there is no correlation. DS: I'm curious to know if you think immune modulators are as useful as antivirals, and if so, when. LW: I think we have to treat HIV disease with a multi-pronged approach, with immune modulators as well as antivirals. The search is on for a good immune modulator. Certainly we know from the research at Stanford that interleukin 2 is a powerful immune stimulant, and I'm very interested in getting involved in some research on that myself. I think the answers are not in yet on Tagamet or Antabuse. DS: Do you share the worry sometimes voiced about immune modulators that taking an immune booster without an antiviral may unwisely promote needless viral replication? LW: If that were true, we'd be seeing more viral replication associated with things like transfer factor; some very elegant Paris studies showed absolutely no signs of stimulating viral replication with transfer factor, yet were able to increase T- cell numbers. So I think that worry has fallen by the wayside. DS: For people in the 500 helper cell range, do you feel that any prophylactic measures, such as against CMV, PCP, Toxoplasma, are worth considering? LW: No. I think the likelihood of them developing those illnesses are so low then, less than 5-10%. But between 200 and 400 helper cells, we administer a skin test to look for immune- cell dysfunction. If the person is anergic, we begin aerosolized pentamidine to protect against Pneumocystis. I believe the reason people get PCP in the higher helper cell ranges is because they have dysfunctional immune systems, and we can select those people without having to treat everybody prophylactically. But I commonly put people who have less than 100 helper cells on clofazimine to see if I can lower the incidence of MAI. Most recently, there has been a movement to try persons with low T- cells on fluconazole as a prophylaxis against cryptococcal meningitis. DS: Anything for toxo or CMV? LW: Other than environmental precautions, no. I check people for toxo titers to see if people have antibodies from a previous exposure. When helper cells get really low, we feel these illnesses are reactivations more than new exposures. But we should, again, say "get tested, get treated, get followed" ...if you find you have a high toxo titer then maybe we should think about putting you on some prophylactic program. There is a wonderful report from Montreal which I know has helped me save a dozen people. It described how survival with toxo is much improved by giving the medicines just twice a week instead of every day, since many people have been lost not to toxo but to the drug toxicity. Just that has been very helpful to me. DS: That reminds me of a letter in the Lancet which suggested that the idea of pulsing AZT once a day might be similarly effective for treating HIV, since bone marrow cells need about 24 hours to generate, so you allow alternating generations of cells to escape some of the damage of AZT. LW: In a sense I've been pulse-dosing AZT every day, having many patients on every 8 hour doses instead of every 4. I really believe that the body needs to recover from the AZT. Unfortunately, studies have shown that even after stopping AZT, bone marrow suppression continued for six weeks. DS: For opportunistic infections, what's new? PCP seems under control ... LW: PCP is well under control, but we have to answer the question of whether oral medications are as effective or more effective than aerosol pentamidine. Toxo is getting good results with pulse-dosing twice a week. MAI may be preventable with clofazimine, 50 mg a day. KS, still a big problem. DS: Really? The options for KS seem so wide-ranging, although that doesn't spell effectiveness. LW: The incidence of KS has dropped, except in the low T-cell ranges, when it is difficult to treat. Even all the options don't necessarily make us more effective. Interferon has a 50-50 chance of working, although higher T-cell counts get a better response to interferon. DS: Anything new for lymphoma or PML? LW: Ivan Silverberg (M. D., of Davies Hospital in San Francisco) has been getting very good results with his chemotherapy, using shorter courses, low doses. He's obtaining good survivals for lymphoma. DS: I spoke to someone at UCSF who was increasing the volume of radiation for treating lymphoma so that the duration of therapy could be shortened. LW: Silverberg has done both with chemo -- decreased the duration and decreased the dose. DS: How about PML? I heard that heparin might be effective, for reasons that are obscure to me. LW: Yes, I heard about that too, at the NIH. Well, heparin keeps coming up -- you know it's a sulfated polysaccharide, like dextran sulfate. It was thought for a while that heparin also would be able to prevent viral (HIV) attachment. I followed some patients who wanted to be treated with heparin, and I didn't see any significant changes. But it keeps coming back, such as this possibility for PML. DS: Something we hear a lot of at AIDS TREATMENT NEWS is instances of people diagnosed with an opportunistic infection, and they or their physician drop the idea of any anti-HIV strategy. Sometimes people will stop AZT for more than six months while they're on Septra, or MAI drugs. If someone is diagnosed with an opportunistic infection, do you stop treating HIV temporarily or do you keep them on an anti-HIV therapy no matter what? LW: I keep them on an anti-HIV therapy. It's important, very important to continue antiviral therapy during treatment for an OI. DS: I'm sure you agree that a lot of things are missing in the world-at-large concerning AIDS treatments, but are there specific glaring gaps that you wish were addressed? LW: Yes. I'm very disturbed that except for the work with compound Q, most of the work seems to be focusing on nucleoside analog therapy. Fine -- we have ddI, ddC, etc. But who is developing ways to kill this virus? Compound Q is a good candidate, but it's only one of six compounds from that family. DS: Given the hubbub over Q, do you think it worthwhile for individuals to consider trying it outside clinical trials, symptomatic or asymptomatic people? LW: Well, I think it will prove to be safe to use for people with over 100 T-cells. With less than 100 there is a great risk of developing disorientation and coma, and they need to be followed very closely by a physician. I have worked on an altered-dosing regimen for those people and have successfully treated about 20 with less than 100 T-cells. We'll need to follow larger numbers to really see if this is true. DS: If you were approached by someone who wanted to try Q, someone who's asymptomatic, with bloodwork relatively stable yet showing some signs of HIV progression, would you ... LW: Give me three months. I think I can answer that question when our new program is under way. The first program addressed dosage and toxicity. Now we need to answer how we use Q over time. ***** PML TREATMENT SURVEY Last year AIDS TREATMENT NEWS (issues #79 & #88) reported the efforts of two activists in Los Angeles to compile a list of possible treatments for a serious AIDS-related viral infection called progressive multifocal leukoencephalopathy (PML). Lisa Muller and Peter Brosnan have sent this list, with periodic updates, to many interested people, and now they are circulating a "PML survey" to collect anecdotal data regarding the effectiveness of various treatments. Peter described some early results of the survey, results which verify what they suspected: "PML is frequently misdiagnosed as Toxo or other central nervous system disorders. Valuable treatment time is thereby lost. Moreover, the actual incidence of PML is, we suspect, vastly underreported and underestimated. Treatment can work -- those people who have received early, aggressive treatment are, in many cases, doing very well. Those people who were sent home to die have done as they were told. We continue hearing good things about both NAC and heparin in the treatment of PML. NAC, especially, seems useful. We have also learned that intrathecal interferon is being tested, but the M. D. 's running the study refuse to comment." Anyone who has PML treatment experience to share can ask for a blank survey by writing Lisa Muller, 3031 Angus St., Los Angeles, CA 90039. Of course, the PML treatment report is still available by sending a request to the same address, or for urgency's sake, by calling 213/666-0751. A donation of $15 helps to pay for copying and express mailings. We commend Lisa and Peter for their ground-breaking work on an infection which has been widely, and wrongly, considered to be untreatable. ***** EMPRISE: CONTROVERSY OVER UNORTHODOX-TREATMENT Database by John S. James On February 14, ACT UP/New York sent AIDS organizations an "Open Letter to the AIDS Community: Stop the Insurance Industry's Blacklist of Unapproved AIDS Treatments," together with a cover letter and five-page background paper by its Alternative and Holistic Treatment Subcommittee. Later, Grace Powers Monaco, president of Emprise, Inc. which is developing the database, sent a 16-page response. The immediate issue is whether the U. S. National Institute of Allergy and Infectious Diseases (NIAID) should give Emprise a grant to compile the computerized listing of "questionable and unproven" AIDS treatments. (NIAID has already given Emprise a $47,000 start-up grant for the project. In 1988, the National Cancer Institute had given Emprise $315,000 to compile a similar database -- not yet available -- of cancer therapies.) We cannot fully cover this complex dispute in a short article. We will provide an outline and brief comments, then refer readers to the organizations involved. The following passages give an example of what the controversy is about. The first is from the ACT UP open letter to the AIDS community, which is currently endorsed by about 20 organizations: "Monaco describes the Emprise project as an effort to warn doctors and patients against 'the dangers and general worthlessness of unproven approaches' -- not to objectively determine which may have merit and are worthy of scientific study. She and her insurance consultant friends will handpick 'expert panels' to practitioners. The cancer panels, already selected, are stacked with sworn enemies of what they label 'health fraud' and 'quackery' -- by which they generally mean: 1) non-FDA approved treatments not produced by the largest, high-profit drug corporations, and 2) doctors who differ from orthodox, 'approved' treatment approaches. An analysis by an advocacy organization from people with cancer concluded that 'serious ethics violations, severe conflicts of interest and a systemic negative bias...permeate this entire project.' In short, the clear goal is to compile a blacklist. "This blacklist will be put on every major medical database used by doctors, and leased to insurance companies to 'assist' them in determining which reimbursement claims to deny. As a federally-funded project, it will also greatly influence Medicaid/Medicare policies and future NIAID/NCI priorities on AIDS clinical trials. Indeed, Emprise explicitly told NIAID, 'The proposed grant will provide sufficient critical and evaluative data to demonstrate which AIDS dubious therapies can be expected to be nonproductive and a bad buy for patients without the expenditure of scarce government resources in a clinical trial to 'disprove' a therapy.'" The ACT UP open letter calls for treatment information developed by community-based clinical trials organizations, not by Emprise. Here is the Emprise response to the section quoted above. It refers first to the cancer database now being developed: "The cancer monographs are now under peer review. If the evaluations by the scientific reviewers hold true through peer review, there are a number of herbal and botanical products and two drugs classed in the safely used adjunctively in cancer treatment and should be put through efficacy screens and potentially studied on clinical trials. The same conclusion was reached about some dietary approaches. Not as cures but as helpful adjuncts. "Although it is not possible to list those products until peer review is finished, as soon as it is, Ms. Monaco will be communicating this information to the Townsend Letter for Doctors, which is a publication for 'alternative' physicians. "Does this sound like a blacklist? "Do you want AIDS patients exposed to true quackery? By shutting Emprise down are you saying that you don't want your constituency to be informed about the scientific misrepresentations by commercialized unproven methods purveyors? "Insurers don't pay for 'worthless' products -- do you want them to? Don't you want to keep scarce resources in enhance the process of finding potentially productive adjuncts to care -- not interfere with it." Background Grace Powers Monaco, an attorney and the president of Emprise, lost a daughter to leukemia in 1970. She is a founding member of Candelighters, a support organization for parents of children with cancer. Ms. Monaco has been one of the most prominent opponents of "health fraud" and "quackery" in cancer, and more recently in AIDS. Since 1978, she "has acted as consulting counsel for insurance companies concerning claims made for treatments which are nonstandard, alternative, unproven, questionable, or experimental, primarily advising on the merits of the claim." She had also been a paid consultant to Aetna Life Insurance Company in a racketeering lawsuit against Stanislaw Burzynski, M. D., developer of the "antineoplaston" cancer drug, but has recused herself from contining that relationship until the antineoplaston monograph (for the cancer-treatment database) has been peer reviewed. But despite these ties to the insurance industry, in her volunteer work for Candelighters, Ms. Monaco has strongly criticized insurance companies for denying reimbursement for treatment such as certain "off-label" uses of chemotherapy which are in fact the accepted standard of care -- a serious problem for persons with cancer, as for persons with AIDS, even when they are seeking only accepted, conventional medical care. Recently some of the alternative-treatment cancer activists who have long been fighting Ms. Monaco met with holistic- treatment AIDS activists to form a coalition to oppose Emprise. A recent meeting (organized by Bob Lederer, co-chair of the Alternative and Holistic Treatment Subcommittee of ACT UP/New York and columnist for Out Week magazine, and Ralph Moss, author of The Cancer Industry) brought together 35 activists from both groups, and laid the groundwork for the ACT UP letter quoted above. Journalists in the cancer group had obtained the Emprise application for the AIDS database pilot study through the Freedom of Information Act; NIAID has not released the application which is now pending. Without the investigation by these journalists, the public would know little about Emprise, as this particular project has had little if any coverage in the general press. Good friends of the AIDS community have spoken out on both sides of this dispute. A recent editorial in PAACNOTES, the newsletter of the Physicians Association for AIDS Care (PAAC), defended the proposed Emprise database because it "could, if funded, provide physicians with peer-reviewed assessments of all available scientific data on the potential value of nutritional supplements, herbals, biologicals and other therapeutic adjuncts, such as imaging and biofeedback. PAAC has supported the need of such a database for physicians who generally have no scientific source to refer to when answering questions from patients on whether these agents or therapies are helpful or harmful. Information about potential drug interaction with alternative therapies is also a critical need of physicians." (Gordon Nary, the author of the above editorial, is well known for his advocacy with the John Alden Life Insurance Company to set up a model program which will pay for care not usually covered by insurance, for example acupuncture or biofeedback for pain control, and nutrients, food, and food preparation for patients at risk for malnutrition. The program saves money for the insurance company by paying for home care, including transportation or reimbursement for care from family members or significant others, when other companies would refuse to cover these expenses and instead pay much more for hospitalization.) But Bernard Bihari, M. D., medical director of the Community Research Initiative in New York, is concerned that the Emprise project could "create a climate in which it is harder to raise money for research, in which researchers are reluctant to test a treatment associated with the label of 'quackery.' The media picks up the most dramatic stories. The result could stifle scientific inquiry and the development of knowledge." Dr. Bihari noted that an early list of potential AIDS treatments attacked by Ms. Monaco was oriented against substances of natural origin -- even while the pharmaceutical industry itself often turns to natural products to find substances which it develops as drugs. (Dr. Bihari does not see insurance as the problem, however, as companies seldom reimburse anyway until after treatments have official sanction.) Comment We are withholding judgment on the Emprise AIDS project at this time. On one hand, we do not see how an unbiased database can come from an organization going into the project with so strongly held an agenda, viewpoint, and commitment as Emprise has in this case. Yet even a negative database could be valuable. For physicians and patients urgently need professional information about all treatments they are considering using. And negative information is often the hardest to find, partly because people are afraid of lawsuits, but even more because usually no one has much motive for researching and publishing the case against a treatment. As a result, the only information available often comes from promoters. Yet not all treatments evolve on the same straight path starting with academic science, proceeding to peer-reviewed articles, and then to competent, rational development by a major pharmaceutical company able to afford the $120 million average development cost per new drug approved in the United States. Treatments which in fact have value can evolve from systems of traditional medicine, from popular culture, or from a scientific or even unscientific hunch. Any treatment which acquires a popular following before acquiring a professional one is at risk of being labeled illegitimate, and then being ignored by institutions and researchers who are fearful of damaging their reputations. Therefore the treatment remains "unproven." We have long suspected that the AIDS movement might best stay away from what could be called "the old wars" -- the unending battles between mainstream medicine and unorthodox treatments for cancer and other diseases. For the old wars have gone on for decades and therefore they are locked into a time scale of decades, while AIDS activists do not have that time. We are concerned that the old wars might now have come to us. Perhaps the best outcome would be for Emprise to produce its database, but do so under a cloud of controversy (fortunately now provided by the open letter from ACT UP/New York). Then the public will know that the project represents not pure Science above the politics of competing views, but rather one view among the others. If the Emprise AIDS database is ever to obtain a reputation for fair and unbiased reporting, then it must earn that reputation. It cannot legitimately be born with it. Note As we went to press, Ms. Monaco told us that because of the controversy Emprise is withdrawing the NIAID grant application, and is working with universities and others to determine how an untested-and-unproven-treatment database could be resubmitted under other auspices, so that the project can proceed with a more collegial relationship. She still feels there is a great need for expert, peer-reviewed critiques of the science alleged to support unproven treatments. She also pointed out that the cancer monographs (on which the AIDS database can be modeled) include suggested future research to answer interesting questions about the proposed treatment -- including the possibility of legitimate uses. For More Information Emprise, Inc. may be able to provide their response to the ACT UP mailing, or other information about the database project. It can be reached at 1312 18th St. NW, Suite 200, Washington, DC 20036. An article by Grace Powers Monaco, "Counseling Patients About Dubious and Rip-Off Remedies for AIDS and ARC," appears in PAACNOTES, May/June 1989, page 80. For the case against the database project, contact ACT UP/New York, Attn. Alternative and Holistic Treatment Subcommittee, 496-A Hudson St., #6-A, New York, NY 10014, 212/989-1114. ***** BURROUGHS WELLCOME SEEKS PROTOCOL-SECRECY LAW A proposed Massachusetts law (bill number S. 464), initiated by Burroughs-Wellcome Co., would make it difficult for the public to obtain protocols for clinical trials, including the informed- consent statements which volunteers entering trials are given to sign. While this particular law would only affect Massachusetts, it could be a precedent for similar legislation elsewhere. The bill, which recently passed one legislative committee despite widespread opposition by AIDS organizations, arose from a dispute between Burroughs Wellcome and ACT UP/Boston over a test of AZT syrup in newborns with HIV-positive mothers. According to Steven Busby of the Community Research Initiative of New England, Burroughs Wellcome had required Boston City Hospital, which conducted the study, not to release any information about it. As a result, even the Massachusetts Department of Public Health (DPH) did not know that the trial was happening, and the study was not listed in the Massachusetts Clinical Trials Registry. ACT UP learned about the study in April 1989. After it proved to the Department of Public Health that the study existed, the DPH requested a copy of the protocol, to which it was legally entitled. Current Massachusetts public-records law allows the release of the protocol to the public. Burroughs-Wellcome claimed that the protocol contained trade secrets, and obtained a temporary injunction to prevent its release. But ACT UP then obtained a copy from the U. S. National Institutes of Health (NIH), which had determined that the protocol did not contain trade secrets, making the injunction moot. Burroughs Wellcome then went to the legislature to change the law for the future. Meanwhile, ACT UP found both ethical and scientific problems with the protocol, and significant changes were made in the study as a result. (According to Busby, NIH policy strongly supports the public release of protocols of drug trials using human subjects if the trials receive public funds, and requires it for phase II studies and above. Opponents of S. 464 could find no other case in which a pharmaceutical company strongly objected to such release; certainly there is no other such case in Massachusetts.) The proposed new law (S. 464) would allow a company required to file a protocol for a clinical trial to claim that the protocol contained trade secrets. If anyone asked for release of the information, a DPH staff person would examine the protocol to decide if there were trade secrets. Either party -- the pharmaceutical company, or the member of the public -- could appeal an unfavorable decision in the courts. Burroughs Wellcome says that this change in the law would give it due-process protection against public release of its proprietary information. But the likely practical effect would be to make it much harder for the public to obtain in-depth information about clinical trials, even if there was in fact no real issue of trade secrets. Companies could routinely claim trade secrets, requiring court action before protocols are released. Litigation favors the richest party, and pharmaceutical companies are usually far better financed than public-interest groups. The result will be to further remove research from public scrutiny. Burroughs Wellcome also says that its bill would make Massachusetts law consistent with Federal law, under which the FDA keeps proprietary drug-testing information confidential. But the proper comparison is with NIH, which routinely requires companies to agree to release protocols of clinical trials as a condition for receiving public funds for those trials. The FDA receives far more detailed and sensitive information from drug companies than ever appears in protocols. Organizations supporting S. 464 include Burroughs Wellcome Co., Massachusetts Biotechnology Council, Inc., Massachusetts Hospital Association, Massachusetts Medical Society, and the Pharmaceutical Manufacturers Association. Legislators are being told that the biotechnology industry fears that competitors might work backward from a protocol to obtain proprietary information. Because of current economic problems, Massachusetts is especially concerned about being attractive to industry. The following organizations are opposed to S. 464: ACT UP/Boston AIDS Action Committee AIDS Watchdog Group Boston AIDS Consortium Children's Hospital AIDS Program Community Research Initiative of New England Dimock Community Health Center Fenway Community Health Center Gay and Lesbian Advocates and Defenders Massachusetts Department of Public Health Massachusetts Law Reform Institute Massachusetts Lesbian and Gay Bar Association Northern Lights Alternative People With AIDS Coalition of Boston Roxbury Comprehensive Health Clinic Note: A December 21 memo from Burroughs Wellcome lists the Massachusetts Department of Public Health as supporting their legislation. In fact the Department opposes the bill, according to Sara Bachrach, it's Director of Government Relations, because it does not want to decrease access by persons with AIDS to information about protocols. A legislative committee ordered the Department to write compromise language for the legislation. The Department did so, but it opposes the bill even with the new language. What You Can Do An attorney opposing the bill, Deborah Thompson of the Massachusetts Law Reform Institute, suggested that persons write to Senator William Keating, Chairman, Steering and Policy Committee, State House Room 413-B, Boston, MA 02133. Even letters from outside Massachusetts, especially from experts, will help show the widespread concern on this issue. For more information, contact Deborah Thompson, Massachusetts Law Reform Institute, 69 Canal St., Boston MA 02114, 617/742-9250. ***** AZT ASYMPTOMATIC STUDY PUBLISHED -- NEW PUSH FOR EARLY DIAGNOSIS, TREATMENT Results of the major U. S. trial of AZT for early intervention in asymptomatic HIV-positive patients (ACTG 019) were published April 5 in the New England Journal of Medicine. The major findings were already known, but physicians have needed more details to guide them in deciding when to recommend AZT. ACTG 019 compared daily doses of 500 mg, 1500 mg, and placebo. AZT clearly reduced progression to AIDS, as well as showing benefit in other measurements, such as T-helper cell increases and p24 antigen reductions. The 500 mg dose not only had lower toxicity than 1500 mg, but also the low dose may have been more effective. For example, the rates of progression to AIDS per 100 person-years were 6.6 with placebo, 2.3 with 500 mg (low dose) of AZT, and 3.1 with 1500 mg. Toxicity not only was less with the lower dose, it was also less for asymptomatic patients than for those more seriously ill. When used in low doses for early treatment, AZT seems not to deserve the reputation for toxicity which it had in the past. For example, there was no statistically significant difference in hematologic toxicity (anemia or neutropenia) or in elevated liver enzymes between the placebo and 500 mg group; nausea (reported by 3.3 percent of the low-dose group vs 0.2 percent on placebo) was the only severe side effect significantly more common with the low dose than with the placebo. (Anemia was found in 1.1 percent of the low-dose group, but was not severe enough in any patient to require a transfusion.) This study re-emphasized the need for people to learn their HIV status and start treatment early. The message is getting out. On March 28 about 300 people had to be turned away from a San Francisco talk by Paul Volberding, M. D., the principal investigator of ACTG 019, on new information about AZT, due to unexpected turnout. The presentation will be repeated in a larger hall on Friday, April 13, at the UCSF Laurel Heights Auditorium, California St. at Presidio, 7:00 - 9:00 PM. These AZT results also highlight the problems of getting treatment to those who cannot afford the price of AZT (currently about $2,200 per year to wholesalers at the 500 mg dose). And even if money is available, many persons with HIV have never had access to primary care; they seek medical treatment in hospital emergency rooms, only when they are very sick. An editorial in the April 5 New England Journal of Medicine ("Early Treatment for HIV: The Time Has Come") commented that "For these persons, the health care needed to provide the demonstrated benefit of early therapy is simply not available. Thus this major advance will result in a cruel and painful irony, and it highlights the urgent need to marshal resources and implement systems of care for all people with HIV infection." ***** KS: INFORMATION NEEDED A statement by Robert Gallo, M. D., of the U. S. National Cancer Institute, suggested that a much-improved potential treatment for KS may have been discovered (see AIDS TREATMENT NEWS #99, March 16, 1990, page 3). But neither Gallo nor anyone else is saying more. We do not know what the drug is, nor what tests have been done. Some rumors are NOT correct: * The report that the drug is "MDS," from the Kowa company, is erroneous. This rumor started when a government press office, which itself did not know the name of the drug, asked a Japanese dermatology expert -- who guessed that it might be "MDS," as he knew that American researchers had been interested in that. In fact, "MDS Kowa" is the name of the most popular brand of dextran sulfate, which is no longer in widespread use as an AIDS treatment. * A report in a Japanese-language newspaper about 26 patients treated successfully with a drug from Japan refers to Kemron -- a low-dose oral interferon tested in Kenya. This research is interesting (see The New York Times, April 4; also see AIDS TREATMENT NEWS #97, February 16, 1990, page 6), but almost certainly it is not what Gallo's lab is studying. * In our last issue we published one physician's guess that the chemical Gallo referred to may be a form of beta cyclodextrin. We have since heard nothing to confirm that this is the drug. If there has been an important advance against KS, why would it be kept secret? There could be many reasons, some more legitimate than others: serious danger of toxicity, supply problems, need to make business arrangements, desire to be published in a medical journal which wants a news splash, or simply business as usual. But even the better reasons do not justify secrecy if it leads to delaysPfor example, by putting all responsibility on a few key people, who are often busy with competing obligations or problems. If something important has been discovered, it should be shared with the public so that others can use their resources and influence to help overcoming obstacles (such as red tape, lack of money, or just being too busy). But people cannot help if they do not know that anything has happened. AIDS TREATMENT NEWS would like to hear, anonymously if necessary, from anybody with treatment information which is too important to be kept secret due to business as usual. ***** STATEMENT OF PURPOSE AIDS TREATMENT NEWS reports on experimental and complementary treatments, especially those available now. It collects information from medical journals, and from interviews with scientists, physicians, and other health practitioners, and persons with AIDS or ARC. Long-term survivors have usually tried many different treatments, and found combinations which work for them. AIDS Treatment News does not recommend particular therapies, but seeks to increase the options available. We also examine the ethical and public-policy issues around AIDS treatment research and treatment access. [Obsolete subscription information has been removed. See the latest issues for up-to-date information. -- sysop] &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display